The aims of our program are to cycle hybrid cells between mouse teratocarcinoma cell and various kinds of differentiated rodent and human cell lines through mice via blastocyst injection in order to trace histochemically their cell lineage and to study the mechanisms controlling gene activity during mammalian development. The in vitro system of integrating genes, chromosome fragments and entire chromosomes into teratocarcinoma cells in combination with the bioassay of introducing these hybrid cells into the living organism allow us to assay for the appearance, coexistence, and regulation of the foreign gene products in the different organs of chimeric mice. We aim to establish (1) whether it is possible to channel the differentiation of the hybrid cells into specific tissues, (2) if nuclear or cytoplasmic factors derived from the parental differentiated cells are responsible for the tissue preference of the hybrid cells and (3) what specific chromosomes are responsible for this phenomenon. We intend to transform thymidine kinase deficient mouse teratocarcinoma cells with recombinant DNA molecules and inject the transformants into mouse blastocysts in order to examine the chimeric tissues for the expression of the foreign DNA sequences.